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U-32,802A

Identifiers
IUPAC name 1-(4-fluorophenyl)-4-amino]butan-1-one
CAS Number	36735-48-5
PubChem CID	hydrochloride: 193243
ChemSpider	hydrochloride: 167691
Chemical and physical data
Formula	C22H23F2NO
Molar mass	355.429 g·mol
3D model (JSmol)	Interactive image hydrochloride: Interactive image
SMILES C1CC(=CCC1NCCCC(=O)C2=CC=C(C=C2)F)C3=CC=C(C=C3)F hydrochloride: C1CC(=CCC1NCCCC(=O)C2=CC=C(C=C2)F)C3=CC=C(C=C3)F.Cl
InChI InChI=1S/C22H23F2NO/c23-19-9-3-16(4-10-19)17-7-13-21(14-8-17)25-15-1-2-22(26)18-5-11-20(24)12-6-18/h3-7,9-12,21,25H,1-2,8,13-15H2 Key:YPJKDDHCJRLZIW-UHFFFAOYSA-N hydrochloride: InChI=1S/C22H23F2NO.ClH/c23-19-9-3-16(4-10-19)17-7-13-21(14-8-17)25-15-1-2-22(26)18-5-11-20(24)12-6-18;/h3-7,9-12,21,25H,1-2,8,13-15H2;1H Key:HWSBEFRRYZIENO-UHFFFAOYSA-N

U-32,802A is an antipsychotic tranquilizer of the butyrophenone class. It was developed by Daniel Lednicer at Upjohn Pharmaceuticals in the early part of the 1970’s. Whereas related agents are based on a 4-aryl-piperidine central ring system, U-32,802A is an 4-aryl-cyclohexylamine, which might be expected to offer a unique pharmacological profile. Based on the available pharmacological data, U-32,802A was hypothesized to act primarily at the presynaptic organelles for storage of monoamines in a way similar to tetrabenazine.

Analogs

Cyclohexylamine butyrophenones

A large number of cyclohexylamine butyrophenones was reported by Lednicer et al.:

1. PC12251406
2. PC83261250 4-(2-Methoxyphenyl)cyclohex-3-en-1-amine,
3. PC37529
4. Benzospirans:
5. 2-amino-5-phenylbicyclononanes
6. PC12230284

4-Arylcyclohexylamines

All four of these designs are also antipsychotics, but they differ in that they were patented by companys other than for Lednicer and employ a different variety of sidechain than was seen above for the butyrophenones. Interestingly, although PC15079631 was listed as an antipsychotic, its mode of auction was to augment dopaminergic neurotransmission and not to inhibit it. This paradoxical mode of antipsychotic action was likewise reported for PD137789 & for PD-158771

1. Pramiverine is an antispasmodic.
2. SIR 117 is an antidepressant.

References

1. Lahti RA, Lednicer D (June 1974). "Effect of a butyrophenone derivative, U-32,802A, on brain biogenic amines". Biochemical Pharmacology. 23 (12): 1701–5. doi:10.1016/0006-2952(74)90397-9. PMID 4842658.
2. Fuenmayor LD, Vogt M (October 1979). "The influence of cerebral 5-hydroxytryptamine on catalepsy induced by brain-amine depleting neuroleptics or by cholinomimetics". British Journal of Pharmacology. 67 (2): 309–18. doi:10.1111/j.1476-5381.1979.tb08681.x. PMC 2043889. PMID 40649.
3. Fuenmayor LD, Vogt M (September 1979). "Production of catalepsy and depletion of brain monoamines by a butyrophenone derivative". British Journal of Pharmacology. 67 (1): 115–22. doi:10.1111/j.1476-5381.1979.tb16114.x. PMC 2043615. PMID 574039.
4. "PC12251406". PubChem. U.S. National Library of Medicine.
5. Lednicer D, Emmert DE (December 1975). "Benzospirans bearing basic substitution. I. Spiro (cyclohexane-1, 2'-indans)". The Journal of Organic Chemistry. 40 (26): 3839–3844. doi:10.1021/jo00914a005.
6. ^ Lednicer D, Emmert DE, Lahti R, Rudzik AD (December 1972). "Partly reduced biphenyls as central nervous system agents. 1. 4-Arylcyclohex-3-enylamines". Journal of Medicinal Chemistry. 15 (12): 1235–8. doi:10.1021/jm00282a008. PMID 4635965.
7. "PC83261250". PubChem. U.S. National Library of Medicine.
8. "PC37529". PubChem. U.S. National Library of Medicine.
9. Lednicer D, Emmert DE, Lahti R, Rudzik AD (December 1972). "Partly reduced biphenyls as central nervous system agents. 2. cis- and trans-4-Arylcyclohexylamines". Journal of Medicinal Chemistry. 15 (12): 1239–43. doi:10.1021/jm00282a009. PMID 4635966.
10. Lednicer D, Emmert DE (December 1975). "Benzospirans bearing basic substitution. II. Amines derived from 3', 4'-dihydrospiro -4-one and 3', 4'-dihydro -4-one". The Journal of Organic Chemistry. 40 (26): 3844–3850. doi:10.1021/jo00914a006.
11. Lednicer D (January 1977). "Butyrophenones from the isomeric 2-amino-5-phenylbicyclononanes". Journal of Medicinal Chemistry. 20 (1): 171–3. doi:10.1021/jm00211a040. PMID 833821.
12. "PC12230284". PubChem. U.S. National Library of Medicine.
13. Lednicer D, Emmert ED, Rudzik AD, Graham BE (June 1975). "Butyrophenones as hypotensive agents. Derivatives of 4-aryl-4-(hydroxymethyl)cyclohexylamine". Journal of Medicinal Chemistry. 18 (6): 593–9. doi:10.1021/jm00240a014. PMID 1151974.
14. "PD137789". Pubchem. U.S. National Library of Medicine.
15. Johnson SJ, Kesten SR, Wise LD (August 1992). "Synthesis of the chiral 4-substituted 1-phenylcyclohexene PD137789 via intramolecular Wittig reaction". The Journal of Organic Chemistry. 57 (17): 4746–9474. doi:10.1021/jo00043a038.
16. Schaus JM, Bymaster FP (January 1998). "Dopaminergic approaches to antipsychotic agents". Annual Reports in Medicinal Chemistry. 33. Academic Press: 1–10. doi:10.1016/S0065-7743(08)61066-0. ISBN 978-0-12-040533-6.
17. "PD-158771". PubChem. U.S. National Library of Medicine.
18. Corbin AE, Meltzer LT, Ninteman FW, Wiley JN, Christoffersen CL, Wustrow DJ, Wise LD, Pugsley TA, Heffner TG (April 2000). "PD 158771, a potential antipsychotic agent with D2/D3 partial agonist and 5-HT(1A) agonist actions. II. Preclinical behavioral effects". Neuropharmacology. 39 (7): 1211–21. doi:10.1016/s0028-3908(99)00214-2. PMID 10760363.

• Butyrophenone antipsychotics
• 4-Fluorophenyl compounds
• Cyclohexenes